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Q99741

- CDC6_HUMAN

UniProt

Q99741 - CDC6_HUMAN

Protein

Cell division control protein 6 homolog

Gene

CDC6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 130 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi202 – 2098ATPSequence Analysis

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. chromatin binding Source: Ensembl
    3. kinase binding Source: BHF-UCL
    4. nucleoside-triphosphatase activity Source: InterPro
    5. nucleotide binding Source: ProtInc
    6. protein binding Source: IntAct

    GO - Biological processi

    1. DNA replication Source: Reactome
    2. DNA replication checkpoint Source: ProtInc
    3. G1/S transition of mitotic cell cycle Source: Reactome
    4. mitotic cell cycle Source: Reactome
    5. mitotic nuclear division Source: UniProtKB-KW
    6. negative regulation of cell proliferation Source: ProtInc
    7. negative regulation of DNA replication Source: ProtInc
    8. positive regulation of chromosome segregation Source: BHF-UCL
    9. positive regulation of cytokinesis Source: BHF-UCL
    10. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
    11. regulation of mitotic metaphase/anaphase transition Source: BHF-UCL
    12. regulation of transcription involved in G1/S transition of mitotic cell cycle Source: Reactome
    13. traversing start control point of mitotic cell cycle Source: ProtInc

    Keywords - Biological processi

    Cell cycle, Cell division, DNA replication, Mitosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_1095. Activation of the pre-replicative complex.
    REACT_111214. G0 and Early G1.
    REACT_1156. Orc1 removal from chromatin.
    REACT_1181. Association of licensing factors with the pre-replicative complex.
    REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_1707. CDC6 association with the ORC:origin complex.
    REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
    REACT_207. Removal of licensing factors from origins.
    REACT_2243. Assembly of the pre-replicative complex.
    REACT_471. E2F mediated regulation of DNA replication.
    REACT_6769. Activation of ATR in response to replication stress.
    REACT_683. G1/S-Specific Transcription.
    SignaLinkiQ99741.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cell division control protein 6 homolog
    Alternative name(s):
    CDC6-related protein
    Cdc18-related protein
    Short name:
    HsCdc18
    p62(cdc6)
    Short name:
    HsCDC6
    Gene namesi
    Name:CDC6
    Synonyms:CDC18L
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:1744. CDC6.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication
    Note: The protein is nuclear in G1 and cytoplasmic in S-phase cells.

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. cytosol Source: Reactome
    3. Golgi apparatus Source: HPA
    4. nucleoplasm Source: Reactome
    5. nucleus Source: BHF-UCL
    6. spindle midzone Source: BHF-UCL
    7. spindle pole Source: BHF-UCL

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Meier-Gorlin syndrome 5 (MGORS5) [MIM:613805]: A syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti323 – 3231T → R in MGORS5. 1 Publication
    VAR_065493

    Keywords - Diseasei

    Disease mutation, Dwarfism

    Organism-specific databases

    MIMi613805. phenotype.
    Orphaneti2554. Ear-patella-short stature syndrome.
    PharmGKBiPA26271.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 560560Cell division control protein 6 homologPRO_0000150979Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei45 – 451Phosphoserine1 Publication
    Modified residuei54 – 541Phosphoserine1 Publication
    Modified residuei127 – 1271Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ99741.
    PaxDbiQ99741.
    PRIDEiQ99741.

    PTM databases

    PhosphoSiteiQ99741.

    Miscellaneous databases

    PMAP-CutDBQ99741.

    Expressioni

    Gene expression databases

    ArrayExpressiQ99741.
    BgeeiQ99741.
    CleanExiHS_CDC6.
    GenevestigatoriQ99741.

    Organism-specific databases

    HPAiHPA050114.
    HPA054703.

    Interactioni

    Subunit structurei

    Interacts with PCNA, ORC1L, cyclin-CDK and HUWE1.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDKN1AP389362EBI-374862,EBI-375077
    CDT1Q9H2113EBI-374862,EBI-456953
    MCM7P339932EBI-374862,EBI-355924

    Protein-protein interaction databases

    BioGridi107426. 43 interactions.
    DIPiDIP-28154N.
    IntActiQ99741. 21 interactions.
    MINTiMINT-1201847.
    STRINGi9606.ENSP00000209728.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2CCHX-ray1.70E/F89-100[»]
    2CCIX-ray2.70F/I71-100[»]
    4I5LX-ray2.43B/E70-90[»]
    4I5NX-ray2.80B/E70-90[»]
    ProteinModelPortaliQ99741.
    SMRiQ99741. Positions 197-233.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ99741.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the CDC6/cdc18 family.Curated

    Phylogenomic databases

    eggNOGiCOG1474.
    HOGENOMiHOG000045316.
    HOVERGENiHBG050860.
    InParanoidiQ99741.
    KOiK02213.
    OMAiPYTRNQI.
    OrthoDBiEOG7QG44J.
    PhylomeDBiQ99741.
    TreeFamiTF101051.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    3.40.50.300. 1 hit.
    InterProiIPR003593. AAA+_ATPase.
    IPR015163. Cdc6_C_dom.
    IPR016314. Cell_div_Cdc6/18.
    IPR027417. P-loop_NTPase.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF09079. Cdc6_C. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001767. Cdc6. 1 hit.
    SMARTiSM00382. AAA. 1 hit.
    SM01074. Cdc6_C. 1 hit.
    [Graphical view]
    SUPFAMiSSF52540. SSF52540. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Q99741-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPQTRSQAQA TISFPKRKLS RALNKAKNSS DAKLEPTNVQ TVTCSPRVKA    50
    LPLSPRKRLG DDNLCNTPHL PPCSPPKQGK KENGPPHSHT LKGRRLVFDN 100
    QLTIKSPSKR ELAKVHQNKI LSSVRKSQEI TTNSEQRCPL KKESACVRLF 150
    KQEGTCYQQA KLVLNTAVPD RLPAREREMD VIRNFLREHI CGKKAGSLYL 200
    SGAPGTGKTA CLSRILQDLK KELKGFKTIM LNCMSLRTAQ AVFPAIAQEI 250
    CQEEVSRPAG KDMMRKLEKH MTAEKGPMIV LVLDEMDQLD SKGQDVLYTL 300
    FEWPWLSNSH LVLIGIANTL DLTDRILPRL QAREKCKPQL LNFPPYTRNQ 350
    IVTILQDRLN QVSRDQVLDN AAVQFCARKV SAVSGDVRKA LDVCRRAIEI 400
    VESDVKSQTI LKPLSECKSP SEPLIPKRVG LIHISQVISE VDGNRMTLSQ 450
    EGAQDSFPLQ QKILVCSLML LIRQLKIKEV TLGKLYEAYS KVCRKQQVAA 500
    VDQSECLSLS GLLEARGILG LKRNKETRLT KVFFKIEEKE IEHALKDKAL 550
    IGNILATGLP 560
    Length:560
    Mass (Da):62,720
    Last modified:May 1, 1997 - v1
    Checksum:i3ED7DE4AF80CB017
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti238 – 2381T → A.1 Publication
    Corresponds to variant rs4135010 [ dbSNP | Ensembl ].
    VAR_019349
    Natural varianti295 – 2951D → N.1 Publication
    Corresponds to variant rs4135012 [ dbSNP | Ensembl ].
    VAR_019350
    Natural varianti299 – 2991T → M.1 Publication
    Corresponds to variant rs4135013 [ dbSNP | Ensembl ].
    VAR_019351
    Natural varianti323 – 3231T → R in MGORS5. 1 Publication
    VAR_065493
    Natural varianti378 – 3781R → H.1 Publication
    Corresponds to variant rs4135016 [ dbSNP | Ensembl ].
    VAR_019352
    Natural varianti441 – 4411V → I.2 Publications
    Corresponds to variant rs13706 [ dbSNP | Ensembl ].
    VAR_019353

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77949 mRNA. Translation: AAB38317.1.
    AF022109 mRNA. Translation: AAC52071.1.
    AY150310 Genomic DNA. Translation: AAN10296.1.
    BC025232 mRNA. Translation: AAH25232.1.
    CCDSiCCDS11365.1.
    RefSeqiNP_001245.1. NM_001254.3.
    UniGeneiHs.405958.

    Genome annotation databases

    EnsembliENST00000209728; ENSP00000209728; ENSG00000094804.
    GeneIDi990.
    KEGGihsa:990.
    UCSCiuc002huj.1. human.

    Polymorphism databases

    DMDMi50400620.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U77949 mRNA. Translation: AAB38317.1 .
    AF022109 mRNA. Translation: AAC52071.1 .
    AY150310 Genomic DNA. Translation: AAN10296.1 .
    BC025232 mRNA. Translation: AAH25232.1 .
    CCDSi CCDS11365.1.
    RefSeqi NP_001245.1. NM_001254.3.
    UniGenei Hs.405958.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2CCH X-ray 1.70 E/F 89-100 [» ]
    2CCI X-ray 2.70 F/I 71-100 [» ]
    4I5L X-ray 2.43 B/E 70-90 [» ]
    4I5N X-ray 2.80 B/E 70-90 [» ]
    ProteinModelPortali Q99741.
    SMRi Q99741. Positions 197-233.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107426. 43 interactions.
    DIPi DIP-28154N.
    IntActi Q99741. 21 interactions.
    MINTi MINT-1201847.
    STRINGi 9606.ENSP00000209728.

    Chemistry

    ChEMBLi CHEMBL2311228.

    PTM databases

    PhosphoSitei Q99741.

    Polymorphism databases

    DMDMi 50400620.

    Proteomic databases

    MaxQBi Q99741.
    PaxDbi Q99741.
    PRIDEi Q99741.

    Protocols and materials databases

    DNASUi 990.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000209728 ; ENSP00000209728 ; ENSG00000094804 .
    GeneIDi 990.
    KEGGi hsa:990.
    UCSCi uc002huj.1. human.

    Organism-specific databases

    CTDi 990.
    GeneCardsi GC17P038443.
    HGNCi HGNC:1744. CDC6.
    HPAi HPA050114.
    HPA054703.
    MIMi 602627. gene.
    613805. phenotype.
    neXtProti NX_Q99741.
    Orphaneti 2554. Ear-patella-short stature syndrome.
    PharmGKBi PA26271.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1474.
    HOGENOMi HOG000045316.
    HOVERGENi HBG050860.
    InParanoidi Q99741.
    KOi K02213.
    OMAi PYTRNQI.
    OrthoDBi EOG7QG44J.
    PhylomeDBi Q99741.
    TreeFami TF101051.

    Enzyme and pathway databases

    Reactomei REACT_1095. Activation of the pre-replicative complex.
    REACT_111214. G0 and Early G1.
    REACT_1156. Orc1 removal from chromatin.
    REACT_1181. Association of licensing factors with the pre-replicative complex.
    REACT_1221. CDK-mediated phosphorylation and removal of Cdc6.
    REACT_1707. CDC6 association with the ORC:origin complex.
    REACT_1949. CDT1 association with the CDC6:ORC:origin complex.
    REACT_207. Removal of licensing factors from origins.
    REACT_2243. Assembly of the pre-replicative complex.
    REACT_471. E2F mediated regulation of DNA replication.
    REACT_6769. Activation of ATR in response to replication stress.
    REACT_683. G1/S-Specific Transcription.
    SignaLinki Q99741.

    Miscellaneous databases

    EvolutionaryTracei Q99741.
    GeneWikii CDC6.
    GenomeRNAii 990.
    NextBioi 4156.
    PMAP-CutDB Q99741.
    PROi Q99741.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q99741.
    Bgeei Q99741.
    CleanExi HS_CDC6.
    Genevestigatori Q99741.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    3.40.50.300. 1 hit.
    InterProi IPR003593. AAA+_ATPase.
    IPR015163. Cdc6_C_dom.
    IPR016314. Cell_div_Cdc6/18.
    IPR027417. P-loop_NTPase.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF09079. Cdc6_C. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001767. Cdc6. 1 hit.
    SMARTi SM00382. AAA. 1 hit.
    SM01074. Cdc6_C. 1 hit.
    [Graphical view ]
    SUPFAMi SSF52540. SSF52540. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase."
      Saha P., Chen J., Thome K.C., Lawlis S.J., Hou Z.H., Hendricks M., Parvin J.D., Dutta A.
      Mol. Cell. Biol. 18:2758-2767(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH PCNA; ORC1 AND CYCLIN-CDK.
    3. NIEHS SNPs program
      Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-238; ASN-295; MET-299; HIS-378 AND ILE-441.
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-441.
      Tissue: Brain.
    5. "Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage."
      Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G.
      Mol. Biol. Cell 18:3340-3350(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUWE1.
    6. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    8. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-127, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. Cited for: VARIANT MGORS5 ARG-323.

    Entry informationi

    Entry nameiCDC6_HUMAN
    AccessioniPrimary (citable) accession number: Q99741
    Secondary accession number(s): Q8TB30
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 130 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3